Wound healing is a process regulated by a complex interaction of multiple growth factors including fibroblast growth factor 2 (FGF2). Although FGF2 appears in several tissue engineered studies, its applications are limited due to its low stability both in vitro and in vivo. Here, this shortcoming is overcome by a unique nine-point mutant of the low molecular weight isoform FGF2 retaining full biological activity even after twenty days at 37 °C. Crosslinked freeze-dried 3D porous collagen/chitosan scaffolds enriched with this hyper stable recombinant human protein named FGF2-STAB® were tested for in vitro biocompatibility and cytotoxicity using murine 3T3-A31 fibroblasts, for angiogenic potential using an ex ovo chick chorioallantoic membrane assay and for wound healing in vivo with 3-month old white New Zealand rabbits. Metabolic activity assays indicated the positive effect of FGF2-STAB® already at very low concentrations (0.01 µg/mL). The angiogenic properties examined ex ovo showed enhanced vascularization of the tested scaffolds. Histological evaluation and gene expression analysis by RT-qPCR proved newly formed granulation tissue at the place of a previous skin defect without significant inflammation infiltration in vivo. This work highlights the safety and biocompatibility of newly developed crosslinked collagen/chitosan scaffolds involving FGF2-STAB® protein. Moreover, these sponges could be used as scaffolds for growing cells for dermis replacement, where neovascularization is a crucial parameter for successful skin regeneration.
Treatment of complete loss of skin thickness requires expensive cellular materials and limited skin grafts used as temporary coverage. This paper presents an acellular bilayer scaffold modified with polydopamine (PDA), which is designed to mimic a missing dermis and a basement membrane (BM). The alternate dermis is made from freeze-dried collagen and chitosan (Coll/Chit) or collagen and a calcium salt of oxidized cellulose (Coll/CaOC). Alternate BM is made from electrospun gelatin (Gel), polycaprolactone (PCL), and CaOC. Morphological and mechanical analyzes have shown that PDA significantly improved the elasticity and strength of collagen microfibrils, which favorably affected swelling capacity and porosity. PDA significantly supported and maintained metabolic activity, proliferation, and viability of the murine fibroblast cell lines. The in vivo experiment carried out in a domestic Large white pig model resulted in the expression of pro-inflammatory cytokines in the first 1–2 weeks, giving the idea that PDA and/or CaOC trigger the early stages of inflammation. Otherwise, in later stages, PDA caused a reduction in inflammation with the expression of the anti-inflammatory molecule IL10 and the transforming growth factor β (TGFβ1), which could support the formation of fibroblasts. Similarities in treatment with native porcine skin suggested that the bilayer can be used as an implant for full-thickness skin wounds and thus eliminate the use of skin grafts.
This study deals with cellulose derivatives in relation to the collagen fibrils in composite collagen-cellulose scaffolds for soft tissue engineering. Two types of cellulose, i.e., oxidized cellulose (OC) and carboxymethyl cellulose (CMC), were blended with collagen (Col) to enhance its elasticity, stability and sorptive biological properties, e.g. hemostatic and antibacterial features. The addition of OC supported the resistivity of the Col fibrils in a dry environment, while in a moist environment OC caused a radical drop. The addition of CMC reduced the mechanical strength of the Col fibrils in both environments. The elongation of the Col fibrils was increased by both types of cellulose derivatives in both environments, which is closely related to tissue like behaviour. In these various mechanical environments, the ability of human adipose-derived stem cells (hADSCs) to adhere and proliferate was significantly greater in the Col and Col/OC scaffolds than in the Col/CMC scaffold. This is explained by deficient mechanical support and loss of stiffness due to the high swelling capacity of CMC. Although Col/OC and Col/CMC acted differently in terms of mechanical properties, both materials were observed to be cytocompatible, with varying degrees of further support for cell adhesion and proliferation. While Col/OC can serve as a scaffolding material for vascular tissue engineering and for skin tissue engineering, Col/CMC seems to be more suitable for moist wound healing, e.g. as a mucoadhesive gel for exudate removal, since there was almost no cell adhesion.
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